V. Guérin

Three months supplementation of hyperhomocysteinaemic patients with folic acid and vitamin B6 improves biological markers of endothelial dysfunction.

Hyperhomocysteinaemia is a risk factor for premature atherosclerosis and venous thromboembolic disease. Supplementation with folic acid and vitamin B6 has been shown to decrease plasma homocysteine but data fail to assess an effect on the progression of vascular disease. We measured plasma homocysteine and two markers of endothelial injury (plasma soluble thrombomodulin and von Willebrand factor) at baseline and after 3 months of treatment with folic acid and vitamin B6. After this treatment there was a significant decrease in fasting soluble thrombomodulin (−15 ng/ml, 95%CI 5–22.2). Von Willebrand factor was significantly raised after methionine load at baseline but did not significantly rise after supplementation.

Endothelial dysfunction during acute methionine load in hyperhomocysteinaemic patients

Hyperhomocysteinaemia has been associated with arterial and venous thrombosis possibly by causing damage to the endothelium. We hypothesised that an oral load in methionine, that increases plasma homocysteine, would also result in an increase in biological markers of endothelial or platelet dysfunction. Then we investigated two groups of patients with arterial or venous occlusive disease: 17 with hyperhomocysteinemia and 12 without hyperhomocysteinemia. We measured in both groups plasma soluble thrombomodulin, von Willebrand factor, P-selectin and tissue factor plasma inhibitor before and 6 hours after a load with 100 mg/kg oral methionine. Methionine load resulted in a significant increase in von Willebrand factor in both groups (P<0.02), suggesting that endothelial dysfunction occurs during the load.

Novel risk factors for premature peripheral arterial occlusive disease in non-diabetic patients: a case-control study.

Background This study aimed to determine the prevalence of genetic and environmental vascular risk factors in non diabetic patients with premature peripheral arterial disease, either peripheral arterial occlusive disease or thromboangiitis obliterans, the two main entities of peripheral arterial disease, and to established whether some of them are specifically associated with one or another of the premature peripheral arterial disease subgroups. Methods and Results This study included 113 non diabetic patients with premature peripheral arterial disease (diagnosis <45-year old) presenting either a peripheral arterial occlusive disease (N = 64) or a thromboangiitis obliterans (N = 49), and 241 controls matched for age and gender. Both patient groups demonstrated common traits including cigarette smoking, low physical activity, decreased levels of HDL-cholesterol, apolipoprotein A–I, pyridoxal 5′-phosphate (active form of B6 vitamin) and zinc. Premature peripheral arterial occlusive disease was characterized by the presence of a family history of peripheral arterial and carotid artery diseases (OR 2.3 and 5.8 respectively, 95% CI), high lipoprotein (a) levels above 300 mg/L (OR 2.3, 95% CI), the presence of the factor V Leiden (OR 5.1, 95% CI) and the glycoprotein Ia807T,837T,873A allele (OR 2.3, 95% CI). In thromboangiitis obliterans group, more patients were regular consumers of cannabis (OR 3.5, 95% CI) and higher levels in plasma copper has been shown (OR 6.5, 95% CI). Conclusions According to our results from a non exhaustive list of study parameters, we might hypothesize for 1) a genetic basis for premature peripheral arterial occlusive disease development and 2) the prevalence of environmental factors in the development of thromboangiitis obliterans (tobacco and cannabis). Moreover, for the first time, we demonstrated that the 807T/837T/873A allele of platelet glycoprotein Ia may confer an additional risk for development of peripheral atherosclerosis in premature peripheral arterial occlusive disease.

Coagulopathies frequency in aseptic osteonecrosis patients.

Many risk factors of aseptic osteonecrosis (AO) are well-known, even if 40% of events are idiopathic. Intravascular thrombosis is one of the physiopathological mechanisms of AO. The aim of this study is to determine the influence of coagulopathies on AO set-up. We performed a prospective case-control study, with 39 cases and 39 controls matched on age and sex. Cases are defined according to radiological criteria, and controls as non-affected by renal or hepatic insuffiency, and without inflammatory syndrome. Well-known AO risk factors were studied. Assessment of thrombosis was based on anti-phospholipid, anti beta2 Glycoprotein I, antiprothrombin, anti-cardiolipin, antithrombin, protein S and C, factor V Leiden, prothrombin gene and MTHFR mutations. 71% of cases presented a classical AO risk factor, vs. 38% of the controls. A significant association was also found between smoking and risk of AO. No significant difference in coagulopathy frequency was shown between cases and controls (56.4% vs. 48.7% respectively, p>0.05). Only abusive consumption of alcohol and tobacco is associated with risk of AO. Our study did not demonstrate any implication of coagulopathies in AO susceptibility. Further studies are needed to investigate more precisely these features.

Thrombose veineuse profonde contemporaine d'une varicelle de l'adulte

INTRODUCTION Some viral infections are associated with deep venous thrombosis. We report a case of deep venous thrombosis in an adult with varicella. He had neither known predisposing factors for thrombosis nor thrombophilia. EXEGESIS Transient significant level of antiphospholipid antibodies and lupus circulating anticoagulant were observed. There was no evidence of thrombophilia. Deep venous thrombosis has been mostly associated with varicella in children. A transient protein S deficiency was present in almost all cases, though it was sometimes related to an anti-protein S antibody. This association is exceptional in adults. Some viruses such as herpesvirus and HIV are responsible for endothelium dysfunction, but this is still unclear in the case of varicella-zoster virus. CONCLUSION In our observation, endothelium activation or antiphospholipid antibodies might be responsible for thrombosis.

Soluble P selectin in systemic sclerosis: relationship with von Willebrand factor, autoantibodies and diffuse or localised/limited disease

A.D. Blann*, J. Constans, P. Carpentier, M. Renard, B. Satger, V. Guerin, M.R. Boisseau, N. Neau-Cransac, C. Conri Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Dudley Road, Birmingham, B18 7QH, UK Service de Medecine Interne et Pathologie Vasculaire, Hopital St Andre, 1 rue Jean Burguet, 33075 Bordeaux, France Service de Medecine Interne et Vasculaire, Hopital de la Tronche, BP217, 38043 Grenoble, France Laboratoire d’Hematologie, Universite Victor Segalen-Bordeaux II, 33076 Bordeaux, France Laboratoire d’Immunologie, Hopital Pellegrin, 33076 Bordeaux, France

Acquired haemophilia A associated with transitory and severe factor V deficiency during bullous pemphigoid: First report

Acquired haemophilia A associated with transitory and severe factor V deficiency during bullous pemphigoid: First report -

Beware of commercial human thrombins used to stimulate cultured endothelial cells.

In the field of in vitro biocompatibility testing, the investigation of cell response at the interface with a biomaterial is of great importance; there is a need for standard conditions and thus of well-defined and reliable sources of materials for an objective evaluation of cellular function. Thrombin is often used in vitro as a stimulating agent to check the specific functions of cultured endothelial cells. In the present work, and in order to select a thrombin of commercial origin, two criteria were borne in mind: purity towards the presence of the von Willebrand factor (vWF) and effectiveness towards vWF release by human umbilical venous endothelial cells (HUVEC) that have been submitted to four human commercial thrombins. We detected the presence of vWF in some thrombin solutions that have not yet been in contact with HUVEC. The different thrombins contained vWF antigen ranging from less than 0.1 mUnit per NIH unit of thrombin (from Diagnostica Stago and Sigma Chemical Co.) to 10-20 mUnit per NIH unit of Fibrindex thrombin (from Ortho Diagnostic Systems). Thus, if vWF is present in commercial thrombins, it contributes to and overestimates the vWF appearance in the media resulting from cell stimulation. Consequently, we fixed on thrombin from Diagnostica Stago for further studies involving HUVEC on biomaterials.